• Je něco špatně v tomto záznamu ?

MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops

E. Isik, K. Shukla, M. Pospisilova, C. König, M. Andrs, S. Rao, V. Rosano, J. Dobrovolna, L. Krejci, P. Janscak

. 2024 ; 10 (6) : eadk2685. [pub] 20240207

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24007169

Transcription-replication conflicts (TRCs) induce formation of cotranscriptional RNA:DNA hybrids (R-loops) stabilized by G-quadruplexes (G4s) on the displaced DNA strand, which can cause fork stalling. Although it is known that these stalled forks can resume DNA synthesis in a process initiated by MUS81 endonuclease, how TRC-associated G4/R-loops are removed to allow fork passage remains unclear. Here, we identify the mismatch repair protein MutSβ, an MLH1-PMS1 heterodimer termed MutLβ, and the G4-resolving helicase FANCJ as factors that are required for MUS81-initiated restart of DNA replication at TRC sites in human cells. This DNA repair process depends on the G4-binding activity of MutSβ, the helicase activity of FANCJ, and the binding of FANCJ to MLH1. Furthermore, we show that MutSβ, MutLβ, and MLH1-FANCJ interaction mediate FANCJ recruitment to G4s. These data suggest that MutSβ, MutLβ, and FANCJ act in conjunction to eliminate G4/R-loops at TRC sites, allowing replication restart.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24007169
003      
CZ-PrNML
005      
20240423155749.0
007      
ta
008      
240412s2024 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1126/sciadv.adk2685 $2 doi
035    __
$a (PubMed)38324687
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Isik, Esin $u Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland $1 https://orcid.org/0000000176358496
245    10
$a MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops / $c E. Isik, K. Shukla, M. Pospisilova, C. König, M. Andrs, S. Rao, V. Rosano, J. Dobrovolna, L. Krejci, P. Janscak
520    9_
$a Transcription-replication conflicts (TRCs) induce formation of cotranscriptional RNA:DNA hybrids (R-loops) stabilized by G-quadruplexes (G4s) on the displaced DNA strand, which can cause fork stalling. Although it is known that these stalled forks can resume DNA synthesis in a process initiated by MUS81 endonuclease, how TRC-associated G4/R-loops are removed to allow fork passage remains unclear. Here, we identify the mismatch repair protein MutSβ, an MLH1-PMS1 heterodimer termed MutLβ, and the G4-resolving helicase FANCJ as factors that are required for MUS81-initiated restart of DNA replication at TRC sites in human cells. This DNA repair process depends on the G4-binding activity of MutSβ, the helicase activity of FANCJ, and the binding of FANCJ to MLH1. Furthermore, we show that MutSβ, MutLβ, and MLH1-FANCJ interaction mediate FANCJ recruitment to G4s. These data suggest that MutSβ, MutLβ, and FANCJ act in conjunction to eliminate G4/R-loops at TRC sites, allowing replication restart.
650    _2
$a lidé $7 D006801
650    12
$a proteiny FANC $x genetika $x metabolismus $7 D051856
650    12
$a R-smyčka $7 D000080870
650    _2
$a DNA-helikasy $x genetika $x metabolismus $7 D004265
650    _2
$a replikace DNA $7 D004261
650    _2
$a DNA $x genetika $7 D004247
655    _2
$a časopisecké články $7 D016428
700    1_
$a Shukla, Kaustubh $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 143 00 Prague, Czech Republic $1 https://orcid.org/0000000179214519
700    1_
$a Pospisilova, Michaela $u Department of Biology and National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A7, Brno 62500, Czech Republic $u International Clinical Research Center, St Anne's University Hospital, Pekarska 53, Brno 656 91, Czech Republic $1 https://orcid.org/0009000934911412
700    1_
$a König, Christiane $u Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland $1 https://orcid.org/0000000273474886
700    1_
$a Andrs, Martin $u Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland $1 https://orcid.org/0000000258501567 $7 xx0315711
700    1_
$a Rao, Satyajeet $u Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland $1 https://orcid.org/0000000175957972
700    1_
$a Rosano, Vinicio $u Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland $1 https://orcid.org/0009000863239031
700    1_
$a Dobrovolna, Jana $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 143 00 Prague, Czech Republic $1 https://orcid.org/0000000324122080
700    1_
$a Krejci, Lumir $u Department of Biology and National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A7, Brno 62500, Czech Republic $u International Clinical Research Center, St Anne's University Hospital, Pekarska 53, Brno 656 91, Czech Republic
700    1_
$a Janscak, Pavel $u Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland $u Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 143 00 Prague, Czech Republic $1 https://orcid.org/0000000217487789
773    0_
$w MED00188818 $t Science advances $x 2375-2548 $g Roč. 10, č. 6 (2024), s. eadk2685
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38324687 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240412 $b ABA008
991    __
$a 20240423155746 $b ABA008
999    __
$a ok $b bmc $g 2081262 $s 1216936
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 10 $c 6 $d eadk2685 $e 20240207 $i 2375-2548 $m Science advances $n Sci Adv $x MED00188818
LZP    __
$a Pubmed-20240412

Najít záznam

Citační ukazatele

    Možnosti archivace